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MRONJ risk associated with combined antiresorptive and vascular endothelial growth factor receptor tyrosine kinase

G Mammone1, R Coropciuc2, T Van den Wyngaert3,4

  • 1Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute and Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven, Belgium.

Bone Reports
|July 2, 2026
PubMed
Abstract

Insights

Concomitant use of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) with bone resorption inhibitors (BRIs) did not independently increase medication-related osteonecrosis of the jaw (MRONJ) risk. Denosumab and smoking were key predictors of MRONJ.

Area of Science:

  • Oncology
  • Pharmacology
  • Oral Surgery

Background:

  • Medication-related osteonecrosis of the jaw (MRONJ) is a potential risk with combined use of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) and bone resorption inhibitors (BRIs).
  • The independent contributions of VEGFR-TKIs, BRI type, and patient factors to MRONJ risk are not fully understood.

Purpose of the Study:

  • To investigate the association between concomitant VEGFR-TKI and BRI use and the risk of developing MRONJ.
  • To identify independent predictors of MRONJ and skeletal-related events (SREs) in patients receiving BRIs.

Main Methods:

  • Retrospective review of patients treated with BRIs, with or without concomitant VEGFR-TKIs.
  • Primary endpoint: MRONJ-free survival. Secondary endpoints: MRONJ incidence and SREs.

Main Results:

  • Concomitant VEGFR-TKI use was not an independent predictor of MRONJ-free survival after adjusting for covariates.
  • Denosumab use and active smoking were identified as independent predictors of MRONJ.
  • VEGFR-TKIs accelerated MRONJ onset in bisphosphonate (BP)-treated patients but not in denosumab-treated patients.
  • MRONJ incidence did not significantly differ between groups, but BRI exposure was shorter in the combination group.

Conclusions:

  • MRONJ risk is influenced by BRI type and individual patient characteristics.
  • Denosumab use is associated with a higher MRONJ risk, irrespective of VEGFR-TKI use.
  • VEGFR-TKIs may hasten MRONJ onset in patients on bisphosphonates, necessitating careful risk-benefit assessment for treatment choices.
Keywords:
BisphosphonatesBone metastasesDenosumabMedication related osteonecrosis of the jawSkeletal related eventsVEGFR-TKIs

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